Tumour microenvironment in sarcoma V1

  • Research type

    Research Study

  • Full title

    Investigating the associations between tumour microenvironmental gene expression, histopathology and survival in soft tissue sarcoma

  • IRAS ID

    266902

  • Contact name

    William R English

  • Contact email

    w.english@sheffield.ac.uk

  • Sponsor organisation

    University of Sheffield

  • Clinicaltrials.gov Identifier

    NCT00423618, ClinicalTrials.gov Identifier; VORTEX-REC-06/MRE03/3, VorteX Biobank REC number

  • Duration of Study in the UK

    9 years, 11 months, 28 days

  • Research summary

    Soft Tissue Sarcoma (STS) are rare cancers of muscle, fat and connective tissue. Survival is less than 25% at 3 years for patients with disease that has spread, or metastasised. Current treatments are limited to radiotherapy and chemotherapy and the identification of new therapies are now urgently needed to improve survival.

    Using publically available genomic data and laboratory models of STS we have identified different molecular signatures associated with increased metastasis and decreased survival. Some of these molecular changes are associated with the generation of different gene variants through a process called mRNA splicing. Genes are temporarily copied into multiple mRNA molecules to allow the gene to be converted in proteins that can control the formation of cells and tissues. mRNA can be rearranged by splicing to allow several proteins to be made from one gene. We have also identified alterations in gene expression between the cancerous STS and the normal cells recruited into the tumour mass, which together are called the tumour microenvironment. Using this data we have been able to tentatively identify subsets of patients that could benefit from newer targeted therapies.

    As STS is a rare cancer, the amount of publically available data is low. The VORTEX phase III trial (NCT00423618), led from the University of Sheffield and the Sheffield Teaching Hospitals Trust, investigated the response of a large number of patients with STS to radiotherapy. Tumour samples and genomic information has been collected and will provide the increased number of patients needed to validate our initial studies. Although patients donated samples to a tissue collection held in Manchester, projects that will use this have to be subjected to ethical review before material and data can be released.

  • REC name

    North West - Greater Manchester East Research Ethics Committee

  • REC reference

    21/NW/0237

  • Date of REC Opinion

    27 Jul 2021

  • REC opinion

    Favourable Opinion